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  • 1
    Publication Date: 2015-06-18
    Description: Cell-to-cell variation is a universal feature of life that affects a wide range of biological phenomena, from developmental plasticity to tumour heterogeneity. Although recent advances have improved our ability to document cellular phenotypic variation, the fundamental mechanisms that generate variability from identical DNA sequences remain elusive. Here we reveal the landscape and principles of mammalian DNA regulatory variation by developing a robust method for mapping the accessible genome of individual cells by assay for transposase-accessible chromatin using sequencing (ATAC-seq) integrated into a programmable microfluidics platform. Single-cell ATAC-seq (scATAC-seq) maps from hundreds of single cells in aggregate closely resemble accessibility profiles from tens of millions of cells and provide insights into cell-to-cell variation. Accessibility variance is systematically associated with specific trans-factors and cis-elements, and we discover combinations of trans-factors associated with either induction or suppression of cell-to-cell variability. We further identify sets of trans-factors associated with cell-type-specific accessibility variance across eight cell types. Targeted perturbations of cell cycle or transcription factor signalling evoke stimulus-specific changes in this observed variability. The pattern of accessibility variation in cis across the genome recapitulates chromosome compartments de novo, linking single-cell accessibility variation to three-dimensional genome organization. Single-cell analysis of DNA accessibility provides new insight into cellular variation of the 'regulome'.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685948/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685948/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Buenrostro, Jason D -- Wu, Beijing -- Litzenburger, Ulrike M -- Ruff, Dave -- Gonzales, Michael L -- Snyder, Michael P -- Chang, Howard Y -- Greenleaf, William J -- 5U54HG00455805/HG/NHGRI NIH HHS/ -- P50 HG007735/HG/NHGRI NIH HHS/ -- P50HG007735/HG/NHGRI NIH HHS/ -- T32 HG000044/HG/NHGRI NIH HHS/ -- T32HG000044/HG/NHGRI NIH HHS/ -- U19 AI057266/AI/NIAID NIH HHS/ -- U19AI057266/AI/NIAID NIH HHS/ -- U54 HG004558/HG/NHGRI NIH HHS/ -- UH2 AR067676/AR/NIAMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2015 Jul 23;523(7561):486-90. doi: 10.1038/nature14590. Epub 2015 Jun 17.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA [2] Program in Epithelial Biology and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA. ; Program in Epithelial Biology and the Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, California 94305, USA. ; Fluidigm Corporation, South San Francisco, California 94080, USA. ; 1] Department of Genetics, Stanford University School of Medicine, Stanford, California 94305, USA [2] Department of Applied Physics, Stanford University, Stanford, California 94025, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/26083756" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cell Compartmentation ; Cell Cycle/genetics ; Cell Line ; Cells/classification/*metabolism ; Chromatin/*genetics/*metabolism ; DNA/genetics/metabolism ; Epigenesis, Genetic ; *Epigenomics ; Genome, Human/genetics ; Humans ; Microfluidics ; Signal Transduction ; Single-Cell Analysis/*methods ; Transcription Factors/metabolism ; Transposases/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
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  • 2
    Publication Date: 2013-10-05
    Description: All known human societies have maintained social order by enforcing compliance with social norms. The biological mechanisms underlying norm compliance are, however, hardly understood. We show that the right lateral prefrontal cortex (rLPFC) is involved in both voluntary and sanction-induced norm compliance. Both types of compliance could be changed by varying the neural excitability of this brain region with transcranial direct current stimulation, but they were affected in opposite ways, suggesting that the stimulated region plays a fundamentally different role in voluntary and sanction-based compliance. Brain stimulation had a particularly strong effect on compliance in the context of socially constituted sanctions, whereas it left beliefs about what the norm prescribes and about subjectively expected sanctions unaffected. Our findings suggest that rLPFC activity is a key biological prerequisite for an evolutionarily and socially important aspect of human behavior.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruff, C C -- Ugazio, G -- Fehr, E -- New York, N.Y. -- Science. 2013 Oct 25;342(6157):482-4. doi: 10.1126/science.1241399. Epub 2013 Oct 3.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory for Social and Neural Systems Research (SNS-Lab), Department of Economics, University of Zurich, Zurich, Switzerland.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24091703" target="_blank"〉PubMed〈/a〉
    Keywords: Adolescent ; Adult ; *Deep Brain Stimulation ; Female ; Humans ; Male ; Prefrontal Cortex/*physiology ; *Social Change ; *Social Responsibility ; Young Adult
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 3
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    American Association for the Advancement of Science (AAAS)
    Publication Date: 1982-09-03
    Description: Increases with aging in subperiosteal dimensions and second moments of area (measures of bending and torsional rigidity) in femoral and tibial cross sections are documented in an archeological sample from the American Southwest. Significant differences between cross-sectional sites and between sexes in the pattern of cortical remodeling with age are also present. These differences appear to be related to variations in the stress or strain levels in different regions of the femur and tibia which result from in vivo mechanical loadings of the lower limb.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruff, C B -- Hayes, W C -- AM00749/AM/NIADDK NIH HHS/ -- AM26740/AM/NIADDK NIH HHS/ -- New York, N.Y. -- Science. 1982 Sep 3;217(4563):945-8.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/7112107" target="_blank"〉PubMed〈/a〉
    Keywords: Adult ; *Aging ; Bone Development ; Female ; Femur/*physiology ; Fractures, Bone/etiology ; Growth ; Humans ; Male ; Middle Aged ; Periosteum/*physiology ; Physical Exertion ; Sex Characteristics ; Stress, Mechanical ; Tibia/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 4
    Publication Date: 1984-09-07
    Description: Four surface antigens previously recognized only in macrophages are present on human small cell lung carcinoma cells and tumors. Cancerous cells may arise from macrophage precursors in bone marrow, and these precursors migrate to lung to participate in the repair of damaged tissue produced by continuous heavy smoking. The characteristic presence of neuropeptides such as bombesin in small cell carcinoma, when considered along with these findings, presents new possibilities for the role of such peptides in nervous, endocrine, and immune system function.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruff, M R -- Pert, C B -- New York, N.Y. -- Science. 1984 Sep 7;225(4666):1034-6.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/6089338" target="_blank"〉PubMed〈/a〉
    Keywords: Antigens, Neoplasm/*analysis ; Antigens, Surface/*analysis ; Carcinoma, Small Cell/etiology/*immunology/pathology ; Cell Line ; Cell Transformation, Neoplastic ; *Hematopoietic Stem Cells ; Humans ; Lung Neoplasms/etiology/*immunology/pathology ; Macrophages/*immunology ; Monocytes/pathology ; Smoking
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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  • 5
    Publication Date: 1985-09-20
    Description: Benzodiazepines, which are widely prescribed for their antianxiety effects, are shown to be potent stimulators of human monocyte chemotaxis. The chemotactic effects of benzodiazepine receptor agonists were blocked by the peripheral benzodiazepine receptor antagonist PK-11195, suggesting that these effects are mediated by the peripheral-type benzodiazepine receptor. Diazepam was also active in inducing chemotaxis. Binding studies on purified monocytes revealed high-affinity peripheral benzodiazepine receptors, and the displacement potencies of various benzodiazepines correlated with their relative potencies in mediating chemotaxis. The demonstration of functional benzodiazepine receptors on human monocytes, together with recent evidence of receptor-mediated monocyte chemotaxis by other psychoactive peptides (such as opiate peptides), suggests a biochemical substrate for psychosomatic communication.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ruff, M R -- Pert, C B -- Weber, R J -- Wahl, L M -- Wahl, S M -- Paul, S M -- New York, N.Y. -- Science. 1985 Sep 20;229(4719):1281-3.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/2994216" target="_blank"〉PubMed〈/a〉
    Keywords: Benzodiazepinones/metabolism/pharmacology ; Binding, Competitive ; Chemotaxis, Leukocyte/*drug effects ; Clonazepam/pharmacology ; Humans ; Isoquinolines/pharmacology ; Monocytes/metabolism/*physiology ; Receptors, GABA-A/analysis/drug effects/*physiology
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
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